Atryn (antithrombin recombinant lyophilized powder for reconstitution)
Company: GTC BioTherapeutics
Approval Status: Approved January 2009
Treatment for: peri-operative and peri-partum thromboembolic events
Areas: Cardiology/Vascular Diseases; Hematology; Trauma/Emergency Medicine
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Atryn is a recombinant antithrombin. Recombinant antithrombin is produced by recombinant DNA technology using genetically engineered goats. The amino acid sequence of recombinant antithrombin is identical to that of human plasma-derived antithrombin. Antithrombin plays a central role in the regulation of hemostasis and is the principal inhibitor of thrombin and Factor Xa5, the serine proteases that play pivotal roles in blood coagulation. Antithrombin neutralizes the activity of thrombin and Factor Xa by forming a complex which is rapidly removed from the circulation.
Atryn is specifically indicated for the prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients.
Atryn is supplied as a powder for reconstitution designed for intravenous administration. The dosage of ATryn is to be individualized based on the patient’s pre-treatment functional antithrombin activity level (expressed in percent of normal) and body weight (expressed in kilograms) and using therapeutic drug monitoring. The goal of treatment is to restore and maintain functional antithrombin activity levels between 80% - 120% of normal (0.8 - 1.2 IU/mL). Treatment should be initiated prior to delivery or approximately 24 hours prior to surgery. Administer loading dose as a 15-minute intravenous infusion, immediately followed by a continuous infusion of the maintenance dose.
Clinical Results
FDA ApprovalFDA approval of Atryn was based on the results of two clinical studies. These single-arm, open-label studies were conducted in 31 ATryn treated hereditary antithrombin (AT) deficient patients and 35 human plasma-derived AT treated hereditary AT deficient patients. The endpoint was non-inferiority in the reduction in the incidence of the occurrence of venous thromboembolic events between the two treatment arms. ATryn was administered as a continuous infusion for at least 3 days, starting one day prior to the surgery or delivery. Plasma AT was administered for at least two days as single bolus infusions. The efficacy was assessed during treatment with AT and up to 7 days after stopping AT treatment. In the human plasma derived AT group, there were 0 incidences of thromboembolic events and in the ATryn treated arm, there was one confirmed diagnosis of an acute deep vein thrombosis (DVT).
Side Effects
Adverse events associated with the use of Atryn may include, but are not limited to, the following:
- Intra-abdominal Hemorrhage
- Application Site Pruritus
- Feeling Hot
- Non-cardiac Chest Pain
- Hepatic Enzyme Abnormal
- Hemarthrosis
Hematuria - Hematoma
Mechanism of Action
Atryn is a recombinant antithrombin. Recombinant antithrombin is produced by recombinant DNA technology using genetically engineered goats into which the DNA coding sequence for human antithrombin has been introduced, along with a mammary gland specific DNA sequence, which directs the expression of the antithrombin into the milk. The amino acid sequence of recombinant antithrombin is identical to that of human plasma-derived antithrombin. Antithrombin plays a central role in the regulation of hemostasis. AT is the principal inhibitor of thrombin and Factor Xa5, the serine proteases that play pivotal roles in blood coagulation. AT neutralizes the activity of thrombin and Factor Xa by forming a complex which is rapidly removed from the circulation.
Literature References
Patnaik MM, Moll S Inherited antithrombin deficiency: a review. Haemophilia 2008;14:1229-39.
Konkle BA, Bauer KA, Weinstein R, Greist A, Holmes HE, Bonfiglio J Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures. Transfusion 2003 March;43(3):390-4
Edmunds T, Van Patten SM, Pollock J et al Transgenically produced human antithrombin: structural and functional comparison to human plasma-derived antithrombin. Blood 1998 June 15;91(12):4561-71
Echelard Y, Meade H, Ziomek C The first biopharmaceutical from transgenic animals: ATryn. Modern Biopharmaceuticals 2005;995-1016
Maclean PS, Tait RC Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs 2007;67(10):1429-40.
Additional Information
For additional information regarding Atryn or the prevention of peri-operative and peri-partum thromboembolic events, please visit the Atryn web page.The FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
